MXPA02006247A - Use of azoles for preventing skin cancer. - Google Patents

Abstract

The invention relates to azoles which are suitable for the prevention of irradiationinduced skin cancer.

Description

USE OF AZOLES FOR THE PREVENTION OF SKIN CANCER Description of the Invention The invention relates to the use of azoles for the prevention of skin cancer caused by radiation. UV radiation is divided according to the corresponding wavelengths in UV-A radiation (320-400 nm, UV-AI: 340-400 nm, UV-A-II: 320-340nm) or UV-B radiation (280-320) nm). In general, it is valid: the harmful action of UV radiation on human skin increases the shorter the wavelength and the longer the duration of the exposure. UV radiation can cause acute and chronic skin damage, depending on the type of radiation wavelength damage. Thus, UV-B radiation can cause from a sunburn (erythema) to more severe skin burns. Reductions in enzymatic activities, alterations in the structure of DNA and alterations of the cell membrane as harmful action of UV-B radiation are also known. UV-A radiations penetrate the deeper layers of the skin and can accelerate the aging process of the skin there. The shorter wave radiation UV-A-II additionally reinforces the formation of sunburn. In addition, UV-A radiation can trigger phototoxic or photoallergic skin reactions. Irradiation very frequent and without protection of the skin REF: 139693 With sunlight it can lead in extreme cases to pathological skin alterations that can go as far as skin cancer. In the fight against tumors are often used ionizing radiation, especially radiation X radiation therapy. "In this regard, not only the affected organ is subjected to a radiation load but also necessarily the skin crossed, which acts harmful and in the worst case can induce skin cancer.A remedy for the prevention of such radiation damage would be very desirable.

Azoles inhibit the growth of normal and cancerous cells in vitro and tumor growth in vivo; see L.R. Benzaquen et al., J.A. (1995) Nat. Med. 1, 534 to 540. It has now been found that azoles are suitable for the prevention of skin cancer induced by radiation. * Radiation-induced "in the sense of the invention means in particular" UV-induced "and" by radiotherapy ".

The invention makes it possible, for example, to produce azole-containing sunscreen agents that totally inhibit or prevent the UV-induced formation of skin cancer, especially of squamous cell carcinomas, basaliomas and malignant melanomas. The object of the invention is therefore the use of azoles for the manufacture of topical agents for the prevention of skin cancer induced by radiation.

Preferred azoles for the prevention of skin cancer correspond, for example, to the formula wherein R means a trifluoro-omethyl, methoxy or o-chloro substituent, see DE-AS 16 70 976. Other preferred azoles comprise, for example, Bifonazole = 1- (4-phenylbenzhydryl) -imidazole Butoconazole = ( +) -1- [4- (4-chlorophenyl) -2- [(2,6-dichlorophenyl) thio] butyl] -1-H-imidazole Croconazole = 1- (1- [2- (3-chlorobenzyloxy) phenyl ] - vinyl) imidazole Clotrimazole = 1- [(2-chlorophenyl) -diphenylmethyl] -1H-imidazole Econazole = 1- [2- (4-chlorobenzyloxy) -2- (2,4-dichlorophenyl) ethyl] imidazole Fenticonazole = 1 - [2- (2,4-dichlorophenyl) -2- [[4- phenylthio] phenyl] methoxy] ethyl] -lH-imidazole Fluconazole = 2- (2, -difluorophenyl) -1,3-bis (1H-1) , 2,4-triazol-1-yl) -2-propanol Isoconazole = 1- [2- (2,4-dichlorophenyl) -2- [(2, 6- dichlorophenyl) methoxy] ethyl] -IH-imidazole Itraconazole (+) -2-sec-butyl-4- [4- (4- t [(2R, 4S) -2- (2,4-dichlorophenyl) -2- (1H, 1,2, -triazole- 1-ylmethyl) -1,3-dioxolan-4-yl-methoxy] phenyl.} Piperazino) phenyl] -2,4-dihydro-3H-l, 2,4-triazol-3-one Ketoconazole (+) - l-acetyl-4-. { 4- [2a- (2,4-dichlorophenyl) -2- (1-imidazolylmethyl) -1,3-dioxolan-4P-ylmethoxy] phenyl Jpiperazine Miconazole = (+) -1- [2- (2, 4-dichlorobenzyloxy) -2- (2,4-dichlorophenyl) ethyl] -lH-imidazole Omoconazole = (Z) -1- [2- [2- (4-chlorophenoxy] -2- (2,4-dichlorophenyl) -1-methylethyl] -lH-imidazole Oxiconazole = (Z) -1- (2,4-dichlorophenyl) -2- (1H-imidazol-1-yl) ethanone-O - [(2, -dichlorophenyl) methyl] oxime Sertaconazole (+) -1- [2,4-dichloro-p- [(7-chlorobenzene [b] thien-3-yl) methoxy] -phenethyl] imidazole Sulconazole = 1- [2- [[(4-chlorophenyl)] methyl] thio] -2- (2,4-dichlorophenyl) ethyl] -1H-imidazole Terconazole = cis-1- [4- [[2- (2,4-dichlorophenyl) -2- (1H-1, 2, -triazol-l-ylmethyl) -1,3-dioxolan-4-yl] methoxy] phenyl] -4- (1-methylethyl) piperazine Tioconazole = (+) -1- [2- (2-chloro-3-thienylmethoxy) -2- (2,4-dichlorophenyl) ethyl] -lH-imidazole The agents according to the invention can be present in the application forms used usually, i.e., as an oil-in-water or water-in-oil emulsion, such as milk, as a lotion, cream, spray, gel. The agents may contain commonly used ingredients, such as, for example, emulsifiers, surface-active compounds, lanolin, petrolatum, water, triglycerides of fatty acids, polyethylene glycols, fatty alcohols, ethoxylated fatty alcohols, fatty acid esters (eg isopropyl palmitate). , isooctyl stearate, diisopropyl ester of adipic acid, etc.), natural or synthetic oils and waxes, pigments (eg titanium dioxide, zinc oxide, gloss pigments, coloring pigments), thickeners (e.g. hydroxyethylcellulose, bentonite, etc.), preservatives, UV absorbers, wetting agents, silicone oils, vitamins, glycerin, ethyl alcohol, essences. The azoles are generally used in amounts of from 0.3 to 30, preferably from 0.5 to 12, in particular from 1 to 6% by weight, based on the finished preparation (agent). The agents according to the invention can be applied and spread on the skin before exposure to radiation. For prolonged irradiation durations, for example in sunbathing, it is recommended to repeat this operation after respective 2 to 3 hours. After an intimate contact with water (baths, showers) the skin must be completely dried and re-coated with the agent according to the invention in case the exposure to radiation should continue. Activity assay Induction of skin tumors by UV irradiation and its reduction in transgenic mice: Group 1: Exposure to UV + eventual sun protection Group 2: Exposure to UV + azole + eventual sun protection Term: Papilloma as expected after 4 a 12 weeks (the development of carcinomas takes about 10 months) The results of both groups indicate that azoles protect against UV-induced skin tumors. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (2)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. Use of azoles for the manufacture of topical agents for the prevention of skin cancer induced by radiation.
2. 2. Use according to claim 1, wherein the azoles are selected from the series of bifonazole, butoconazole, clotrimazole, croconazole, econazole, fenticonazole, fluconazole, isoconazole, itraconazole, ketoconazole, miconazole, omoconazole, oxiconazole, sertaconazole, sulconazole, terconazole, thioconazole, and their mixtures.